An autoimmune disease occurs when the body's immune system attacks and destroys healthy body tissue. There are as many as 80 types of autoimmune diseases, such as systemic lupus erythematosus (SLE), multiple sclerosis (MS) and rheumatoid arthritis (RA) as common autoimmune diseases in the northern hemisphere affecting an increasing number of patients. Autoimmune diseases are, thus, an enormous global problem that significantly threatens human health. Known treatment options for autoimmune diseases focus on relieving the symptoms as there is no curative therapy available.
There is increasing evidence that auto-reactive T cells contribute to the development of such diseases. Th1, Th2, Th17 and T regulatory (Treg) cells are CD4+ T cell subsets. More specifically, naive CD4+ T cells will differentiate into T helper (Th1, Th2, Th9, Th17) and T regulatory (Treg) cells to execute their functional activities depending on the cytokines in the local environment. They can be characterized by their cytokine profile and by transcription factors. Besides Th1, Th17 are also mainly involved in the progress of autoimmune diseases. Thus, inhibiting IL-17 production has been regarded as a new strategy to treat autoimmune diseases. It is well known the retinoic acid-related orphan nuclear receptor γt (ROR-γt)/RORγ2 is a main regulator of interleukin 17 (IL-17)-producing helper T (Th17) cell development.
Limonin (Limonoate D-ring-lactone) is a member of a group of chemically related triterpene derivatives also known as limonoids found in the Rutaceae and Meliaceae families. It has been reported that Limonin has a broad spectrum of biological activities on insects including insecticidal, insect anti-feedant and growth regulating activity, and it has demonstrated a range of pharmacological properties on humans such as anti-bacterial, anti-fungal, anti-viral, anti-inflammatory and anti-cancer efficiency (Battinelli L. et al., Planta Med. 2003, 69(10): 910-3, Yoon, Y. C. et al., Molecules. 2015, 20(12):22128-36, Breksa, A. P. and Manners, G. D., J Agric Food Chem. 2006, 54(11):3827-31, Zhang, A. et al., Food Funct. 2015, 6(11): 3540-9, Zunino, S. J. et al., Nutr Res. 2016, 36(1):24-30, Eraky, M. A. et al., Parasitol Res. 2016, 115(10): 4045-54).
As the incidence of autoimmune disease is still rising and as treatment options are limited, there remains a strong need for further methods and compounds for treating autoimmune diseases. Such methods should preferably allow for treating such diseases with a reduced risk of side effects. Respective compounds should be easily obtainable.